Mucosal immunization with purified ClpP could elicit protective efficacy against pneumococcal pneumonia and sepsis in mice.
Caseinolytic protease (ClpP) has been found to be highly conserved among different strains of Streptococcus pneumoniae and intraperitoneal immunization with ClpP could elicit protection against invasive pneumococcal infections. In this study, mucosal immunization with ClpP antigen induced both systemic and mucosal antibodies, and in this way reduced lung colonization in an invasive pneumococcal pneumonia model and also protected mice against death in an intraperitoneal-sepsis model. Surface localization of ClpP was confirmed using flow cytometry analysis. Furthermore, characterization of human sera for anti-ClpP IgG antibody levels demonstrated that ClpP protein was immunogenic in healthy children and was expressed during disease based on the elevated antibody levels in infected individuals. Finally, we describe that in vitro functional anti-ClpP antibody could kill streptococcus pneumoniae by polymorphonuclear leukocytes in a complement-dependent assay. To our knowledge, this is the first study about the protective efficacy of mucosal immunization with ClpP as a promising pneumococcal protein antigen.
Cao
Ju
J
Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, #1 Yixueyuan Road, ChongQing 400016, PR China.
Chen
Tingmei
T
Li
Dairong
D
Wong
Chun K
CK
Chen
Dapeng
D
Xu
Wenchun
W
Zhang
Xuemei
X
Lam
Christopher W K
CW
Yin
Yibing
Y
D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology*; D001769:Blood / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003165:Complement System Proteins / Q000276:immunology; D049071:Endopeptidase Clp; D005260:Female; D006801:Humans; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D009092:Mucous Membrane / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D022242:Pneumococcal Vaccines / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000517:prevention & control*; D018805:Sepsis / Q000276:immunology / Q000517:prevention & control*; D012697:Serine Endopeptidases / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology; D016019:Survival Analysis
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D022242:Pneumococcal Vaccines; D003165:Complement System Proteins; D012697:Serine Endopeptidases; C501427:ClpP protein, Streptococcus pneumoniae; D049071:Endopeptidase Clp